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miRNA, affects both pre- and postsynaptic function to couple changes in
the activity of the muscle to that of the motor neuron (
Simon
et al
., 2008
).
In the muscle,
mir-1
decreases sensitivity to acetylcholine (ACh) by target-
ing two subunits of the nicotinic ACh receptor, while in the motor neuron,
it exerts a non-cell-autonomous effect mediated through a retrograde signal
from the muscle that results in decreased ACh release. As opposed to
promoting a transition, as proposed for mir-124 in the
Aplysia
sensory-
motor synapse,
mir-1
is likely to be mediating a homeostatic response to
refine the activity of the nematode NMJ. At the
Drosophila
larva NMJ, the
mir-310-313
cluster also plays a role in regulating synaptic strength, likely
allowing for the establishment of synaptic homeostasis as well. The
mir-310
cluster negatively regulates synaptic strength at the NMJ during larval
development when synaptic growth is fast, likely to promote homeostatic
compensation (
Tsurudome
et al
., 2010
). In contrast to
mir-1
in the worm,
the
mir-310
cluster exerts its function in the motor neuron, not in the
muscle. In the neuron, it inhibits expression of a kinesin family member,
Khc-73
, which plays a role in recruiting specific proteins to the presynaptic
active zones.
As mentioned, the regulation of apoptosis is essential during the devel-
opment and maturation of the nervous system. It is well known that during
their maturation, neurons that establish successful connections become
decreasingly sensitive to apoptosis induced by a number of insults.
miRNA profiling of developing sympathetic neurons revealed that mir-29
levels are significantly increased in mature neurons compared to developing
ones (
Kole
et al
., 2011
). This increase is not limited to sympathetic neurons;
it is also observed in cerebellar and cortical neurons during their maturation.
In neuronal cultures, mir-29 has been shown to repress the apoptotic
pathway by targeting at least four different BH3-only inducers of apoptosis.
In the developing retina of
Xenopus
, mir-24a plays a similar role in restrict-
ing apoptosis through repression of the proapoptotic factors
caspase 9
and
apaf1
(
Walker and Harland, 2009
)
.
A summary of the different stages of neuronal development and the
discussed miRNAs acting at each stage is presented in
Fig. 5.1
.
2.2. miRNAs in glia development
Glial cells account for at least half of the cells in the human brain and their
functions range from providing structural support, regulating the balance
of water, ions, and nutrients in the brain and maintaining the blood-brain
barrier, to providing the myelin sheaths that are so essential for neuro-
nal conduction and even modulating neuronal synaptic transmission
(for review, see the Nature Insight on Glia issue, editorial by
Chouard
and Gray, 2010
). Glial cells derive from the same NPCs that give rise to
neurons, through a similar series of stages. Perhaps not surprisingly at this
